Antioxidant Supplementation in the Treatment of Aging-Associated Diseases

Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented

Sirtuin 1 and Aging Theory for Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary disease (COPD) is an inflammatory syndrome that represents an increasing health problem, especially in the elderly population. Drug therapies are symptomatic and inadequate to contrast disease progression and mortality. Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets. Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD. Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD. The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes. Recent evidence corroborating the statement of the "aging theory for COPD" was also discussed

Persistent itching associated to silodosin in an elderly patient: Implications for drug-drug interactions and pharmacogenetics

Itching is a complaint affecting especially the elderly, in whom comorbidities and polypharmacy increase the risk of adverse drug reactions. We reported the case of an 83-year-old man with a generalized itching lasting more than 3 years underwent to our attention during his enrollment in a clinical study at University Hospital of Salerno, Italy where he was planned for a thromboendoarteriectomy because of left internal carotid artery stenosis. His medical history included arterial hypertension, ischemic heart disease, chronic cerebrovasculopathy, dyslipidaemia and prostatic hyperplasia. His therapy was olmesartan medoxomil 10 mg/die, nebivolol 5 mg x 1/2/die, acetylsalicylic acid 100 mg/die, omeprazole 20 mg/die, atorvastatin 20 mg/die, supplements contain ing EPA and DHA, vitamins K2, B6, B12 and folic acid (vit B9) and silodosin 8 mg/die. The patient’s demographic clinic, laboratory data and a pharmacological anamnesis were collected. Screening of two ABCB1 polymorphisms associated to a decrease of P-glycoprotein (P-gp) activity was performed by realtime PCR. An iatrogenic cause of the itching was suspected and the Naranjo algorithm was applied, revealing possible association between such an adverse reaction and all used drugs. Because the patient reported the beginning of the itching in concomitance with the aspirin assumption, this agent was discontinued but without improvement. Then, because silodosin-atorvastatin interaction may increase the silodosin plasma concentration, this drug was switched to doxazosin and the itching disappeared. This clinical case stresses the potential misleading based on the patients’ beliefs and the importance to consider all the patients’ available information to ascertain the cause of adverse drug reactions

Biomarkers to personalize the treatment of rheumatoid arthritis: Focus on autoantibodies and pharmacogenetics

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is very complex and heterogeneous. If not adequately treated, RA patients are likely to manifest excess of morbidity and disability with an important impact on the quality of life. Pharmacological treatment is based on the administration of the disease-modifying antirheumatic drugs (DMARDs), subdivided into conventional synthetic (csDMARDs), targeted synthetic (tsDMARDs), and biological (bDMARDs). bDMARDs are now frequently administered in patients, both as alternative treatment and together with csDMARDs. Unfortunately, there is a therapeutic response variability both to old and new drugs. Therefore, to identify pre-therapeutic and on-treatment predictors of response is a priority. This review aims to summarize recent advances in understanding the causes of the variability in treatment response in RA, with particular attention to predictive potential of autoantibodies and DMARD pharmacogenetics. In recent years, several biomarkers have been proposed to personalize the therapy. Unfortunately, a magic bullet does not exist, as many factors concur to disease susceptibility and treatment outcomes, acting around the patient’s congenital background. Models integrating demographic, clinical, biochemical, and genetic data are needed to enhance the predictive capacity of specific factors singularly considered to optimize RA treatment in light of multidisciplinary patient management

Migration and Localization of Metal Atoms on Strained Graphene

Reconstructed point defects in graphene are created by electron irradiation and annealing. By applying electron microscopy and density functional theory, it is shown that the strain field around these defects reaches far into the unperturbed hexagonal network and that metal atoms have a high affinity to the nonperfect and strained regions of graphene. Metal atoms are attracted by reconstructed defects and bonded with energies of about 2 eV. The increased reactivity of the distorted π-electron system in strained graphene allows us to attach metal atoms and to tailor the properties of graphene.Peer reviewe

Antioxidant Supplementation Hinders the Role of Exercise Training as a Natural Activator of SIRT1

Exercise training (ET) is a natural activator of silent mating type information regulation 2 homolog 1 (SIRT1), a stress-sensor able to increase the endogenous antioxidant system. SIRT1 activators include polyphenols and vitamins, the antioxidant properties of which are well-known. Antioxidant supplements are used to improve athletic performance. However, they might blunt ET-related benefits. Middle-distance runners (MDR) taking (MDR-S) or not taking antioxidant supplements (MDR-NoS) were compared with each other and with sedentary subjects (CTR) to evaluate the ET effects on SIRT1 levels and oxidative stress, and to investigate whether an exogenous source of antioxidants could interfere with such effects. Thirty-two MDR and 14 CTR were enrolled. MDR-S took 240 mg vitamin C and 15 mg vitamin E together with mineral salts. SIRT1 mRNA and activity were measured in PBMCs. Total oxidative status (TOS) and total antioxidant capacity (TEAC) were determined in plasma. MDR showed higher levels of SIRT1 mRNA (p = 0.0387) and activity (p = 0.0055) than did CTR. MDR-NoS also showed higher levels than did MDR-S without reaching statistical significance. SIRT1 activity was higher (p = 0.0012) in MDR-NoS (1909 ± 626) than in MDR-S (1276 ± 474). TOS did not differ among the groups, while MDR showed higher TEAC levels than did CTR (2866 ± 581 vs. 2082 ± 560, p = 0.0001) as did MDR-S (2784 ± 643) and MDR-NoS (2919 ± 551) (MDR-S vs. CTR, p = 0.0007 and MDR-NoS vs. CTR, p = 0.003). TEAC (β = 0.4488356, 95% CI 0.2074645 0.6902067; p < 0.0001) and the MDR-NoS group (β = 744.6433, 95% CI 169.9954 1319.291; p= 0.012) predicted SIRT1 activity levels. Antioxidant supplementation seems to hinder the role of ET as a natural activator of SIRT1

SIRT1 activity in peripheral blood mononuclear cells correlates with altered lung function in patients with chronic obstructive pulmonary disease

Background. Oxidative stress is a recognized pathogenic mechanism in chronic obstructive pulmonary disease (COPD). Expression of the NAD+-dependent deacetylase Sirtuin 1 (SIRT1), an antiaging molecule with a key role in oxidative stress response, has been described as decreased in the lung of COPD patients. No studies so far investigated whether systemic SIRT1 activity was associated to decreased lung function in this disease. Methods. We measured SIRT1 protein expression and activity in peripheral blood mononuclear cells (PBMCs) and total oxidative status (TOS), total antioxidant capacity (TEAC), and oxidative stress index (TOS/TEAC) in the plasma of 25 COPD patients, 20 healthy nonsmokers (HnS), and 20 healthy smokers (HS). Results. The activity of SIRT1 was significantly lower in COPD patients compared to both control groups while protein expression decreased progressively (HnS > HS > COPD). TOS levels were significantly lower in HnS than in smoke-associated subjects (COPD and HS), while TEAC levels were progressively lower according (HnS > HS > COPD). In COPD patients, SIRT1 activity, but not protein levels, correlated significantly with both lung function parameters (FEV1/FVC and FEV1) and TEAC. Conclusions. These findings suggest loss of SIRT1-driven antioxidant activity as relevant in COPD pathogenesis and identify SIRT1 activity as a potential convenient biomarker for identification of mild/moderate, stable COPD

Performance and Comparison of Lithium-Ion Batteries Under Low-Earth-Orbit Mission Profiles

The performance of two 28 V, 25 Ah lithium-ion batteries is being evaluated under low-Earth-orbit mission profiles for satellite and orbiter applications. The batteries are undergoing life testing and have achieved over 12,000 cycles to 40 percent depth-of-discharge

NASA Aerospace Flight Battery Program: Generic Safety, Handling and Qualification Guidelines for Lithium-Ion (Li-Ion) Batteries; Availability of Source Materials for Lithium-Ion (Li-Ion) Batteries; Maintaining Technical Communications Related to Aerospace Batteries (NASA Aerospace Battery Workshop)

This NASA Aerospace Flight Battery Systems Working Group was chartered within the NASA Engineering and Safety Center (NESC). The Battery Working Group was tasked to complete tasks and to propose proactive work to address battery related, agency-wide issues on an annual basis. In its first year of operation, this proactive program addressed various aspects of the validation and verification of aerospace battery systems for NASA missions. Studies were performed, issues were discussed and in many cases, test programs were executed to generate recommendations and guidelines to reduce risk associated with various aspects of implementing battery technology in the aerospace industry. This document contains Part 1 - Volume I: Generic Safety, Handling and Qualification Guidelines for Lithium-Ion (Li-Ion) Batteries, Availability of Source Materials for Lithium-Ion (Li-Ion) Batteries, and Maintaining Technical Communications Related to Aerospace Batteries (NASA Aerospace Battery Workshop)

Improving the productivity of millet based cropping systems in the West African Sahel: Experiences from a long-term experiment in Niger

Resource-poor farmers who are living in the harsh environments of the West African Sahel (WAS) depend on subsistence orientated, low-input farming systems for meeting their livelihood needs. These largely extractive farming systems have resulted in nutrient depletion, soil fertility decline, low productivity and land degradation. A study conducted over 25 years in Niger, aimed to evaluate the long-term effects of organic and mineral fertilizers, cropping systems (CS) of millet and cowpea on crop productivity. The traditional millet/cowpea intercrop system without P fertilizer (TrM/C) was compared with four improved CS receiving P fertilizer: sole millet (MM), millet/cowpea intercrop (M/C), millet-cowpea rotation (M-C), and M/C and rotation with cowpea (M/CC). Nitrogen fertilizer (N) and the residues of millet (CR) were applied alone or in combination in all five cropping systems. CR were always applied as mulch. The traditional system (TrM/C) produced the lowest millet grain yields (GY) (0.02–0.43 t/ha). All the four improved CS (MM, M/C, M-C and M/C-C) increased GY compared with the traditional system (TrM/C). The M/C and MM systems increased millet GY 3 and 3.3 times compared with the TrM/C, respectively. The M/C-C and M-C systems produced 4 and 4.2 times more GY than that of the TrM/C system, respectively. The lowest revenue was obtained with the TrM/C system. Except for the TrM/C, the revenue of the MM system was lower compared with combined cultivation of millet and cowpea. Compared with the TrM/C system, M/C and M/C-C provided 2 times more revenue. By providing 2.4 times more revenue than the TrM/C system, the M-C system was the most productive system. Cowpea provided from 54% and 56% of the revenue in M/C-C and M-C system, respectively. Soil organic carbon decreased in all the CS from 46% to 63% compared with the soil kept under natural vegetation fallow. The improved CS increased soil P from 3.4 to 4 times. Over the 25 years of cropping, the highest millet yields were obtained with the lower levels of rainfall indicating the role of nutrients in the system. The four improved systems maintained millet yields over the 25 years of cropping. By improving water and nutrient use efficiency, integrated management of mineral fertilizers, CR and cowpea affected more crop productivity than the rainfall. We concluded that cereal-legume based cropping systems treated with small doses of mineral fertilizers and CR could be used for sustainable management of soil fertility in low-input farming systems